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Serial Inflammatory Cytokine Levels Are Increased in Atrial Fibrillation after Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Circulation(2022)

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摘要
Introduction: Chimeric Antigen receptor T- Cells (CAR-T) are novel therapy for various malignancies, including lymphoma. Cardiotoxicity such as heart failure, arrhythmia, and acute coronary syndrome frequently occurs in the setting of cytokine release syndrome (CRS). Hypothesis: We aimed to investigate the changes in inflammatory cytokines in patients who develop cardiotoxicity after CAR-T therapy. Methods: This was a prospective observational cohort study involving patients diagnosed with lymphoma treated with CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel). Serum cytokines interleukin (IL)-2, IL-6, IL-15, IFN-gamma, TNF-alpha, GM-CSF, and angiopoietin 1 & 2 were tested before lymphodepletion and daily during index hospitalization. Cytokines were analyzed using the ELLA Immunoassay system (SimplePlex, Protein Simple) and reported in pg/mL. Cardiac events were adjudicated by a cardio-oncology team. Results: Fifty-three patients with a complete set of cytokine levels were analyzed. There were 9 cardiac events after CAR-T (8 atrial fibrillation and 1 cardiomyopathy). Patients with cardiac events were older and had higher baseline creatinine level and left atrial volume. All cardiac events occurred in patients who had low-grade CRS (5 Grade 1 and 4 Grade 2 CRS). Tocilizumab was given to seven patients. Pre-CAR-T baseline inflammatory cytokine levels were not different in the cardiac event group. However, median peak IFN-gamma, IL-6, and IL-15 levels were higher median in the cardiac event group (Figure 1). Conclusions: In the setting of CAR-T, the elevation of multiple pro-inflammatory pathways from cytokine release syndrome may be related to the adverse cardiac events, including atrial fibrillation. Further studies are needed to identify and investigate the role of specific inflammatory mediators in cardiac events after CAR-T therapy.
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